To preserve the integrity of the corneal epithelium it is essential to maintain a transparent and refractile medium. Persistent epithelial defects and recurrent cornea erosions are painful and may occur if the integrity of the corneal surface is challenged by injury or disease. Epithelial healing becomes compromised when disorders in the adhesion of corneal epithelial cells are prevalent. The overall goal of this proposal is to examine interactions between epithelial cells and their underlying extracellular matrix. We have shown that these interactions influence the localization and expression of adhesion proteins. Specifically, the aims of the project are to: 1). analyze the regulation of adhesion and cytoskeletal proteins by corneal substrata, 2). analyze changes in cytoplasmic pH and Ca2+ in vitro in response to changes in substrata and 3). analyze the role of phosphorylation in cell-matrix interactions. The adhesion assay developed by the applicant will be used as a vehicle to examine these interactions. To achieve the aims we will analyze the expression of adhesion receptors and intracellular signalling events on mechanically altered, chemically altered and photoablate corneal substrata. The responses will be correlated with changes in the formation of adhesion structures and cytoarchitecture. By understanding the interactions between epithelial cells and their substrate, one can develop new modes of therapy aimed at indolent epithelial defects of the cornea.